The benzisothiazole compound with which the present invention is concerned has been given the USAN name of tiospirone. The hydrochloride salt has been referred to in the prior art as BMY-13859-1 and also as tiospirone. Other acid addition salts thereof are named by combining "tiospirone" with the appropriate word to define the acid form which it is prepared as in "tiospirone hydrochloride". The latter is the U.S. adopted name (USAN) which was recommended by the U.S. Pharmacopeial Convention, Inc.
The synthesis of the compound and disclosure of its antipsychotic properties are described in the following patent and representative publications.
1. Temple, Jr., et al., U.S. Pat. No. 4,411,901 issued Oct. 25, 1983. PA1 2. Annual Reports in Medicinal Chemistry: Vol. 21 (1986) pp. 1-9; Vol. 22 (1987) pp. 1-10. PA1 3. Eison, et al., BMY-13859. Drugs of the Future 1985; 10(9): 773-2. PA1 4. Kurtz, et al., "Review of pre-clinical and clinical pharmacology of tiaspirone an atypical antipsychotic", NCDEU Abstract 1987. PA1 Ergot Alkaloids, PA1 Beta-blocking Agents, PA1 Calcium Channel Blocking Agents, PA1 Antidepressants, and PA1 Mixtures of these.
Vascular headache is a recognized category of headache classification which generally is understood to contain migraine and cluster headaches due to a vascular implication in their etiology. Currently, it is thought possible that muscle-contraction headaches also contain a vascular component in their etiology and may therefore be considered as vascular-related. Additionally there are headaches which are classified as "combined" or "mixed" since they appear to be muscular and vascular-type occurring together. For a good current summary of headache and its treatment, see: Chapter 13: "Drugs Used to Treat Migraine and Other Headaches" in Drug Evaluations, 6th Edition, 1986, pp. 239-252, American Medical Association, W.B. Saunders Co., Phil., PA.
Drugs most commonly used in treatment of headache fall into the following groups:
Management of recurring vascular headache is complicated by the lack of a single therapy which is effective in all patients with the same headache type and by the need to select either an abortive or prophylactic method of treatment for these headaches. Further complication involves the current use of drugs that cause dependence with extended use, such as ergotamine. Another important consideration for the present invention is that the more effective antimigraine agents in current use, e.g. the ergots, methysergide, produce severe use-limiting side-effects with long term usage.
In short, there is no reliable method of treatment for patients afflicted with the more severe type of headache, classified as vascular headache. Further, there is nothing in the prior art to suggest the method of the present invention--that tiospirone would effectively alleviate such headaches, particularly when tiospirone bears no structural resemblance to any therapeutic agent accepted as being useful in the treatment of vascular headaches.
The objectives of the present invention have been to provide effective relief from the pain associated with vascular or vascular-related headache; to give prophylactic protection against headache episodes; to provide abortive therapy; and to provide headache relief using an agent not associated with drug dependence.